In an effort to understand the biology of nerve growth factor (NGF) we have developed an "experimental autoimmune approach" whereby we can deprive a developing (prenatal and postnatal) or mature animal of NGF. Adult rats, rabbits or guinea pigs (g. pigs) immunized with mouse NGF develop antibodies (anti-NGF) which cross-react with their own NGF. Atrophy and death of the sympathetic neurons are seen in these animals. Immunized females pass the cross-reacting antibodies to their fetuses. NGF deprivation of the fetus produces massive destruction of the sympathetic and sensory nervous systems. Animals with gross sensory deficits can be produced. This is the first demonstration that sensory neurons require NGF for survival in vivo, and that in utero exposure to maternal antibodies can cause permanent developmental defects. This approach may be useful to study the physiological role of other putative growth factors. We now plan to examine systematically the effects of prenatal NGF deprivation on a variety of cells of neural crest origin (e.g., various components of the sympathetic, enteric, and sensory systems) by biochemical (neurotransmitter, neuropeptides), morphological (morphometry, immunohistochemistry), and physiological (nerve muscle preps, whole nerve bundle recordings) methods. We will try to expand the approach to other species and to reduce variability by examining inbred strains of animals, and to examine the physiological roles of other putative neurotrophic factors. After the effects of NGF deprivation on the fetus is better clarified and optimal strains and species defined, we will determine when (at what stage) in development NGF deprivation results in the observed loss of neurons. We will attempt to correlate electrophysiological and biochemical changes in the sensory nervous systems of animals deprived of NGF in utero, and to examine the possibility that NGF deprivation results in meuropathy in adult animals who make antibodies against their own NGF. These studies will increase our understanding of the biological roles of NGF and the possible role of NGF "deprivation" in disease. The studies will also provide baseline data useful in the application of this experimental approach to the study of other "growth factors."